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Vaccine Detail
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CTB-MUC1-Alum-CpG Vaccine |
| Vaccine Information |
- Vaccine Name: CTB-MUC1-Alum-CpG Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Subunit vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 12-mer MUC1 (APDTRPAPGSTA) (Lu et al., 2015)
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Adjuvant:
CpG ODN 1826; Alum (Lu et al., 2015)
- Immunization Route: subcutaneous injection
- Description: A recombinant protein vaccine in which a 12-amino acid MUC1 peptide (APDTRPAPGSTA), derived from the N-terminal portion of the MUC1 VNTR tandem repeat, is inserted via replacement of the predicted B cell epitope region (Q56–D59) of the cholera toxin B subunit (CTB), expressed in E. coli TG1 periplasm and purified via His-tag affinity chromatography (~25 mg per liter, >90% pure). Among four candidate insertion positions tested, Q56–D59 yielded the closest-to-native MUC1 conformation. The inserted MUC1 peptide presents as a flexible surface-exposed loop on pentameric CTB-MUC1 (5×12-mer per pentamer, one per monomer), more closely approximating native tumor-expressed MUC1 conformation than N- or C-terminal fusion or chemical conjugate approaches. Formulated with aluminum hydroxide (Alum, 0.3 mg/dose) and CpG ODN 1826 (30 µg/dose) and administered subcutaneously. Subcutaneous immunization of C57BL/6 mice (50 µg/dose, days 0, 14, 28) induced MUC1-specific CTLs with 59.6% lysis of MUC1+B16 target cells at 50:1 effector:target ratio compared to ~30% in controls (p<0.05), a ~2-fold increase in CD8+ T cell proliferation, a ~5-fold increase in CD8+IFNγ+ lymphocytes, and elevated IgG2c/IgG1 ratio indicating Th1 polarization. CTB-MUC1-Alum-CpG significantly reduced tumor burden in prophylactic MUC1+B16 melanoma challenge while other groups showed no tumor inhibitory activity. Tumor-infiltrating lymphocyte analysis showed ~10-fold and ~15-fold increases in CD3e and CD8a mRNA respectively, with ~5-fold increases in Th1-associated markers (IFNγRβ, CCR2, IL-2Rα, CCR5). In therapeutic settings (30 µg/dose, days 7, 13, 20), CTB-MUC1-Alum-CpG significantly inhibited tumor growth compared to control groups receiving CTB-irrelevant peptide (CTB-irrel)-CpG or chemically conjugated CTB-MUC1-Alum-CpG (Lu et al., 2015).
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| Host Response |
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| References |
Lu et al., 2015: Lu W, Qiu L, Yan Z, Lin Z, Cao M, Hu C, Wang Z, Wang J, Yu Y, Cheng X, Cao P, Li R. Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit. Oncotarget. 2015; 6(33); 34537-34548. [PubMed: 26417929].
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